Synthesis and antifungal activity of nitrophenyl-pyrazole substituted Schiff bases

Three new pyrazole-based azomethine isomers (2a-c) bearing a 2-, 3- or 4-nitrophenyl substituent were prepared in almost quantitative yields using environmentally friendly techniques such as solvent-free and microwave-assisted procedures. The compounds were fully characterized by standard analytical methods, including single-crystal X-ray diffraction crystallography for two of the three synthesized compounds. The calculated molecular orbitals distributions of the HOMO and LUMO show that the band gap energy can be tuned by the addition of a nitrophenyl group on the pyrazole moiety and therefore the electrophilic character and the reactivity of the Schiff bases. The relative position of the nitro group plays an important role on the antifungal activity against C. albicans as compound bearing the 2-nitrophenyl substituent (2a) was considerably more active than the other derivatives. In contrast, all three isomers presented a similar, limited, activity against C. neoformans. Molecular docking simulations showed that the most active compound 2a presented the lowest binding energy with 3PVK model protein. (C) 2021 Elsevier B.V. All rights reserved.

Automated summary

In this study, three new pyrazole-based azomethine isomers were synthesized using environmentally friendly techniques. The addition of a nitrophenyl group on the pyrazole moiety was found to tune the band gap energy and reactivity, leading to increased antifungal activity against C. albicans for the compound bearing the 2-nitrophenyl substituent. Molecular docking simulations also confirmed the strong binding affinity of the most active compound with a model protein.